Long term efficacy and safety of cyclosporin versus parenteral gold in early rheumatoid arthritis: a three year study of radiographic progression, renal function, and arterial hypertension.

OBJECTIVE: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment. METHODS: The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage. Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure. RESULTS: Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group. The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%. CONCLUSION: Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients.

Progression of joint damage in early active severe rheumatoid arthritis during 18 months of treatment: comparison of low-dose cyclosporin and parenteral gold.

OBJECTIVE: This study compared the progression of joint damage in patients with early active severe rheumatoid arthritis (RA) treated with cyclosporin or parenteral gold. METHODS: In this open, randomized, multicentre study with a blinded radiological endpoint, 375 patients who had suffered from active severe RA for <3 yr were randomized to be treated for 18 months with low-dose cyclosporin or parenteral gold. The groups were stratified with regard to corticosteroid use. Primary efficacy variables were numbers of erosions, erosion score and the Larsen-Dale joint damage score. RESULTS: Joint damage progressed at similar rates in both treatment arms. In both groups, patients receiving corticosteroids had less X-ray progression. Rheumatoid factor positivity, high swollen joint count, high erythrocyte sedimentation rate and pre-existing X-ray abnormalities predicted progression of joint damage. Although numbers of serious adverse events were similar, more gold patients (n = 65) than cyclosporin patients (n = 45) withdrew from study medication because of adverse events. CONCLUSION: Cyclosporin was comparable to parenteral gold in retarding progression of joint damage and was better tolerated in terms of adherence to therapy. The open label design should be kept in mind when assessing this difference.